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From Snake Venom’s Disintegrins and C-Type Lectins to Anti-Platelet Drugs

1
School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
2
Department of Bioengineering, College of Engineering, Temple University, Philadelphia, PA 19122, USA
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(5), 303; https://doi.org/10.3390/toxins11050303
Received: 25 April 2019 / Revised: 16 May 2019 / Accepted: 24 May 2019 / Published: 27 May 2019
(This article belongs to the Special Issue From Toxins to Drugs)
Snake venoms are attractive natural sources for drug discovery and development, with a number of substances either in clinical use or in research and development. These drugs were developed based on RGD-containing snake venom disintegrins, which efficiently antagonize fibrinogen activation of αIIbβ3 integrin (glycoprotein GP IIb/IIIa). Typical examples of anti-platelet drugs found in clinics are Integrilin (Eptifibatide), a heptapeptide derived from Barbourin, a protein found in the venom of the American Southeastern pygmy rattlesnake and Aggrastat (Tirofiban), a small molecule based on the structure of Echistatin, and a protein found in the venom of the saw-scaled viper. Using a similar drug discovery approach, linear and cyclic peptides containing the sequence K(R)TS derived from VP12, a C-type lectin protein found in the venom of Israeli viper venom, were used as a template to synthesize Vipegitide, a novel peptidomimetic antagonist of α2β1 integrin, with anti-platelet activity. This review focus on drug discovery of these anti-platelet agents, their indications for clinical use in acute coronary syndromes and percutaneous coronary intervention based on several clinical trials, as well as their adverse effects. View Full-Text
Keywords: snake venom; Tirofiban; Eptifibatide; Vipegitide; anti-platelet drug; acute coronary syndrome; percutaneous coronary intervention; clinical trial; adverse effect snake venom; Tirofiban; Eptifibatide; Vipegitide; anti-platelet drug; acute coronary syndrome; percutaneous coronary intervention; clinical trial; adverse effect
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Lazarovici, P.; Marcinkiewicz, C.; Lelkes, P.I. From Snake Venom’s Disintegrins and C-Type Lectins to Anti-Platelet Drugs. Toxins 2019, 11, 303.

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